Skip to main content

Advertisement

Log in

Current Concepts and Controversies in Prevention and Treatment of Diabetic Ketoacidosis in Children

  • Treatment of Type 1 Diabetes (D Dabelea, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Diabetic ketoacidosis (DKA) is caused by absolute or relative lack of insulin. Lack of insulin leads to hyperglycemia, ketonemia, and acidosis. Prevalence of DKA at diagnosis of type 1 diabetes (T1D) varies around the world from 18 % to 84 %. Incidence of recurrent DKA is higher among females, insulin pump users, those with a history of psychiatric or eating disorder, and suboptimal socioeconomic circumstances. DKA is the most common cause of death in children with T1D. Children with DKA should be treated in experienced centers. Initial bolus of 10–20 mL/kg 0.9 % saline is followed by 0.45 %-0.9 % saline infusion. Fluid infusion should precede insulin administration (0.1 U/kg/h) by 1–2 hours. The prevention of DKA at diagnosis of diabetes can be achieved by an intensive community intervention and education of health care providers to raise awareness. Prevention of recurrent DKA requires continuous patient education and access to diabetes programs and telephone services.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Wolfsdorf J, Glaser N, Sperling MA. Diabetic ketoacidosis in infants, children, and adolescents: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:1150–9.

    Article  PubMed  Google Scholar 

  2. Kitabchi AE, Umpierrez GE, Murphy MB, Kreisberg RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care. 2006;29:2739–48.

    Article  PubMed  CAS  Google Scholar 

  3. Dunger DB, Sperling MA, Acerini CL, et al. ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents. Arch Dis Child. 2004;89:188–94.

    Article  PubMed  CAS  Google Scholar 

  4. Rewers A, Klingensmith G, Davis C, et al. Diabetes ketoacidosis at onset of diabetes: the SEARCH for diabetes in Youth Study. Diabetes. 2007;54 Suppl 1:A63–4.

    Google Scholar 

  5. Bui H, To T, Stein R, Fung K, Daneman D. Is diabetic ketoacidosis at disease onset a result of missed diagnosis? J Pediatr. 2009;156:472–7.

    Google Scholar 

  6. Hekkala A, Knip M, Veijola R. Ketoacidosis at diagnosis of type 1 diabetes in children in Northern Finland: temporal changes over 20 years. Diabetes Care. 2007;30:861–6.

    Article  PubMed  CAS  Google Scholar 

  7. Neu A, Hofer SE, Karges B, Oeverink R, Rosenbauer J, Holl RW. Ketoacidosis at diabetes onset is still frequent in children and adolescents: a multicenter analysis of 14,664 patients from 106 institutions. Diabetes Care. 2009;32:1647–8.

    Article  PubMed  Google Scholar 

  8. Karges B, Neu A, Hofer SE, et al. Frequency and influencing factors of ketoacidosis at diabetes onset in children and adolescents–a long-term study between 1995 and 2009. Klin Padiatr. 2011;223:70–3.

    Article  PubMed  CAS  Google Scholar 

  9. Oyarzabal IM, Garcia CB, Barrio CR, et al. Ketoacidosis at onset of type 1 diabetes mellitus in pediatric age in Spain and review of the literature. Pediatr Endocrinol Rev. 2012;9:669–71.

    Google Scholar 

  10. Levy-Marchal C, Patterson CC, Green A. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study. European and Diabetes. Diabetologia. 2001;44 Suppl 3:B75–80.

    Article  PubMed  Google Scholar 

  11. Bui TP, Werther GA, Cameron FJ. Trends in diabetic ketoacidosis in childhood and adolescence: a 15-year experience. Pediatr Diabetes. 2002;3:82–8.

    Article  PubMed  Google Scholar 

  12. Jackson W, Hofman PL, Robinson EM, Elliot RB, Pilcher CC, Cutfield WS. The changing presentation of children with newly diagnosed type 1 diabetes mellitus. Pediatr Diabetes. 2001;2:154–9.

    Article  PubMed  CAS  Google Scholar 

  13. Abdul-Rasoul M, Habib H, Al-Khouly M. 'The honeymoon phase' in children with type 1 diabetes mellitus: frequency, duration, and influential factors. Pediatr Diabetes. 2006;7:101–7.

    Article  PubMed  Google Scholar 

  14. bdul-Rasoul M, Al-Mahdi M, Al-Qattan H, et al. Ketoacidosis at presentation of type 1 diabetes in children in Kuwait: frequency and clinical characteristics. Pediatr Diabetes. 2010;11:351–6.

    Article  Google Scholar 

  15. Al Rashed AM. Pattern of presentation in type 1 diabetic patients at the diabetes center of a university hospital. Ann Saudi Med. 2011;31:243–9.

    Article  PubMed  Google Scholar 

  16. Levy-Marchal C, Papoz L, de Beaufort C, et al. Clinical and laboratory features of type 1 diabetic children at the time of diagnosis. Diabet Med. 1992;9:279–84.

    Article  PubMed  CAS  Google Scholar 

  17. Komulainen J, Kulmala P, Savola K, et al. Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes Care. 1999;22:1950–5.

    Article  PubMed  CAS  Google Scholar 

  18. Mallare JT, Cordice CC, Ryan BA, Carey DE, Kreitzer PM, Frank GR. Identifying risk factors for the development of diabetic ketoacidosis in new onset type 1 diabetes mellitus. Clin Pediatr. 2003;42:591–7.

    Article  Google Scholar 

  19. Rewers A, Chase HP, Mackenzie T, et al. Predictors of acute complications in children with type 1 diabetes. JAMA. 2002;287:2511–8.

    Article  PubMed  Google Scholar 

  20. Pinkey JH, Bingley PJ, Sawtell PA, Dunger DB, Gale EA. Presentation and progress of childhood diabetes mellitus: a prospective population-based study. The Bart's-Oxford Study Group. Diabetologia. 1994;37:70–4.

    Article  PubMed  CAS  Google Scholar 

  21. Levine BS, Anderson BJ, Butler DA, Antisdel JE, Brackett J, Laffel LM. Predictors of glycemic control and short-term adverse outcomes in youth with type 1 diabetes. J Pediatr. 2001;139:197–203.

    Article  PubMed  CAS  Google Scholar 

  22. Childhood Diabetes Research Groups. How frequently do children die at the onset of Insulin-Dependent Diabetes Mellitus? Analyses of registry data from Japan, Poland, the Netherlands, and Allegheny Co., PA. Diab Nutr Metab. 1990;3:57–62.

    Google Scholar 

  23. Edge JA, Ford-Adams ME, Dunger DB. Causes of death in children with insulin dependent diabetes 1990–1996. Arch Dis Child. 1999;81:318–23.

    Article  PubMed  CAS  Google Scholar 

  24. Curtis JR, To T, Muirhead S, Cummings E, Daneman D. Recent trends in hospitalization for diabetic ketoacidosis in Ontario children. Diabetes Care. 2002;25:1591–6.

    Article  PubMed  Google Scholar 

  25. Lawrence SE, Cummings EA, Gaboury I, Daneman D. Population-based study of incidence and risk factors for cerebral edema in pediatric diabetic ketoacidosis. J Pediatr. 2005;146:688–92.

    Article  PubMed  Google Scholar 

  26. Edge JA, Hawkins MM, Winter DL, Dunger DB. The risk and outcome of cerebral oedema developing during diabetic ketoacidosis. Arch Dis Child. 2001;85:16–22.

    Article  PubMed  CAS  Google Scholar 

  27. Glaser N, Barnett P, McCaslin I, et al. Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics. N Engl J Med. 2001;344:264–9.

    Article  PubMed  CAS  Google Scholar 

  28. Mahoney CP, Vlcek BW, DelAguila M. Risk factors for developing brain herniation during diabetic ketoacidosis. Pediatr Neurol. 1999;21:721–7.

    Article  PubMed  CAS  Google Scholar 

  29. •• Glaser N. Cerebral injury and cerebral edema in children with diabetic ketoacidosis: could cerebral ischemia and reperfusion injury be involved? Pediatr Diabetes. 2009;10:534–41. This paper provides possible explanation of the mechanism of cerebral edema in the course of DKA.

    Article  PubMed  CAS  Google Scholar 

  30. Blamire AM, Anthony DC, Rajagopalan B, Sibson NR, Perry VH, Styles P. Interleukin-1beta -induced changes in blood-brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. J Neurosci. 2000;20:8153–9.

    PubMed  CAS  Google Scholar 

  31. Hoffman WH, Burek CL, Waller JL, Fisher LE, Khichi M, Mellick LB. Cytokine response to diabetic ketoacidosis and its treatment. Clin Immunol. 2003;108:175–81.

    Article  PubMed  CAS  Google Scholar 

  32. Nadler OA, Finkelstein MJ, Reid SR. How well does serum bicarbonate concentration predict the venous pH in children being evaluated for diabetic ketoacidosis? Pediatr Emerg Care. 2011;27:907–10.

    Article  PubMed  Google Scholar 

  33. •• Sottosanti M, Morrison GC, Singh RN, et al. Dehydration in children with diabetic ketoacidosis: a prospective study. Arch Dis Child. 2012;97:96–100. This study underlines difficulty in a clinical or laboratory assessment of the degree of dehydration in children with diabetic ketoacidosis.

    Article  PubMed  Google Scholar 

  34. Fagan MJ, Avner J, Khine H. Initial fluid resuscitation for patients with diabetic ketoacidosis: how dry are they? Clin Pediatr. 2008;47:851–5.

    Article  Google Scholar 

  35. Poirier MP, Greer D, Satin-Smith M. A prospective study of the "two-bag system'' in diabetic ketoacidosis management. Clin Pediatr. 2004;43:809–13.

    Article  Google Scholar 

  36. Felner EI, White PC. Improving management of diabetic ketoacidosis in children. Pediatrics. 2001;108:735–40.

    Article  PubMed  CAS  Google Scholar 

  37. Adrogue HJ, Barrero J, Eknoyan G. Salutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis. Use in patients without extreme volume deficit. JAMA. 1989;262:2108–13.

    Article  PubMed  CAS  Google Scholar 

  38. Van Zyl DG, Rheeder P, Delport E. Fluid management in diabetic-acidosis–Ringer's lactate versus normal saline: a randomized controlled trial. QJM. 2012;105:337–43.

    Article  PubMed  Google Scholar 

  39. Savas-Erdeve S, Berberoglu M, Oygar P, et al. Efficiency of fluid treatments with different sodium concentration in children with type 1 diabetic ketoacidosis. J Clin Res Pediatr Endocrinol. 2011;3:149–53.

    Article  PubMed  Google Scholar 

  40. Burghen GA, Etteldorf JN, Fisher JN, Kitabchi AQ. Comparison of high-dose and low-dose insulin by continuous intravenous infusion in the treatment of diabetic ketoacidosis in children. Diabetes Care. 1980;3:15–20.

    Article  PubMed  CAS  Google Scholar 

  41. Kitabchi AE. Low-dose insulin therapy in diabetic ketoacidosis: fact or fiction? Diabetes Metab Rev. 1989;5:337–63.

    Article  PubMed  CAS  Google Scholar 

  42. Edge JA, Jakes RW, Roy Y, et al. The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children. Diabetologia. 2006;49:2002–9.

    Article  PubMed  CAS  Google Scholar 

  43. Kapellen T, Vogel C, Telleis D, Siekmeyer M, Kiess W. Treatment of diabetic ketoacidosis (DKA) with 2 different regimens regarding fluid substitution and insulin dosage (0.025 vs 0.1 units/kg/h). Exp Clin Endocrinol Diabetes. 2012;120:273–6.

    Article  PubMed  CAS  Google Scholar 

  44. Puttha R, Cooke D, Subbarayan A, et al. Low dose (0.05 units/kg/h) is comparable with standard dose (0.1 units/kg/h) intravenous insulin infusion for the initial treatment of diabetic ketoacidosis in children with type 1 diabetes-an observational study. Pediatr Diabetes. 2010;11:12–7.

    Article  PubMed  CAS  Google Scholar 

  45. Al HS, Shann F. Insulin infused at 0.05 vs 0.1 units/kg/hr in children admitted to intensive care with diabetic ketoacidosis. Pediatr Crit Care Med. 2011;12:137–40.

    Article  Google Scholar 

  46. Adrogue HJ, Lederer ED, Suki WN, Eknoyan G. Determinants of plasma potassium levels in diabetic ketoacidosis. Medicine. 1986;65:163–72.

    PubMed  CAS  Google Scholar 

  47. •• Chua HR, Schneider A, Bellomo R. Bicarbonate in diabetic ketoacidosis - a systematic review. Ann Intensive Care. 2011;1:23. This extensive review of existing evidence supports current recommendation regarding role of bicarbonate in treatment of DKA.

    Article  PubMed  Google Scholar 

  48. Muir AB, Quisling RG, Yang MC, Rosenbloom AL. Cerebral edema in childhood diabetic ketoacidosis: natural history, radiographic findings, and early identification. Diabetes Care. 2004;27:1541–6.

    Article  PubMed  Google Scholar 

  49. Glasgow AM. Devastating cerebral edema in diabetic ketoacidosis before therapy. Diabetes Care. 1991;14:77–8.

    PubMed  CAS  Google Scholar 

  50. Curtis JR, Bohn D, Daneman D. Use of hypertonic saline in the treatment of cerebral edema in diabetic ketoacidosis (DKA). Pediatr Diabetes. 2001;2:191–4.

    Article  PubMed  CAS  Google Scholar 

  51. • Seewi O, Vierzig A, Roth B, Schonau E. Symptomatic cerebral oedema during treatment of diabetic ketoacidosis: effect of adjuvant octreotide infusion. Diabetol Metab Syndr. 2010;2:56. This paper provides a new therapeutic options for treatment of cerebral edema.

    Article  PubMed  Google Scholar 

  52. Bosnak M, Dikici B, Dogru O, Davutoglu M, Haspolat K. Somatostatin therapy in the management of resistant diabetic ketoacidosis. Diabetes Care. 2002;25:629–30.

    Article  PubMed  CAS  Google Scholar 

  53. Tasker RC, Lutman D, Peters MJ. Hyperventilation in severe diabetic ketoacidosis. Pediatr Crit Care Med. 2005;6:405–11.

    Article  PubMed  Google Scholar 

  54. Marcin JP, Glaser N, Barnett P, et al. Factors associated with adverse outcomes in children with diabetic ketoacidosis-related cerebral edema. J Pediatr. 2002;141:793–7.

    Article  PubMed  Google Scholar 

  55. Hoffman WH, Steinhart CM, el Gammal T, Steele S, Cuadrado AR, Morse PK. Cranial CT in children and adolescents with diabetic ketoacidosis. AJNR Am J Neuroradiol. 1988;9:733–9.

    PubMed  CAS  Google Scholar 

  56. Glaser NS, Wootton-Gorges SL, Buonocore MH, et al. Frequency of sub-clinical cerebral edema in children with diabetic ketoacidosis. Pediatr Diabetes. 2006;7:75–80.

    Article  PubMed  Google Scholar 

  57. Rewers A, McFann K, Chase HP. Bedside monitoring of blood beta-hydroxybutyrate levels in the management of diabetic ketoacidosis in children. Diabetes Technol Ther. 2006;8:671–6.

    Article  PubMed  CAS  Google Scholar 

  58. Byrne HA, Tieszen KL, Hollis S, Dornan TL, New JP. Evaluation of an electrochemical sensor for measuring blood ketones. Diabetes Care. 2000;23:500–3.

    Article  PubMed  CAS  Google Scholar 

  59. Wallace TM, Meston NM, Gardner SG, Matthews DR. The hospital and home use of a 30-second hand-held blood ketone meter: guidelines for clinical practice. Diabet Med. 2001;18:640–5.

    Article  PubMed  CAS  Google Scholar 

  60. Guerci B, Benichou M, Floriot M, et al. Accuracy of an electrochemical sensor for measuring capillary blood ketones by fingerstick samples during metabolic deterioration after continuous subcutaneous insulin infusion interruption in type 1 diabetic patients. Diabetes Care. 2003;26:1137–41.

    Article  PubMed  CAS  Google Scholar 

  61. Hoffman WH, O'Neill P, Khoury C, Bernstein SS. Service and education for the insulin-dependent child. Diabetes Care. 1978;1:285–8.

    Article  PubMed  CAS  Google Scholar 

  62. Drozda DJ, Dawson VA, Long DJ, Freson LS, Sperling MA. Assessment of the effect of a comprehensive diabetes management program on hospital admission rates of children with diabetes mellitus. Diabetes Educ. 1990;16:389–93.

    Article  PubMed  CAS  Google Scholar 

  63. Grey M, Boland EA, Davidson M, Li J, Tamborlane WV. Coping skills training for youth with diabetes mellitus has long-lasting effects on metabolic control and quality of life. J Pediatr. 2000;137:107–13.

    Article  PubMed  CAS  Google Scholar 

  64. Svoren BM, Butler D, Levine BS, Anderson BJ, Laffel LM. Reducing acute adverse outcomes in youths with type 1 diabetes: a randomized, controlled trial. Pediatrics. 2003;112:914–22.

    Article  PubMed  Google Scholar 

  65. Laffel LM, Wentzell K, Loughlin C, Tovar A, Moltz K, Brink S. Sick day management using blood 3-hydroxybutyrate (3-OHB) compared with urine ketone monitoring reduces hospital visits in young people with T1DM: a randomized clinical trial. Diabet Med. 2006;23:278–84.

    Article  PubMed  CAS  Google Scholar 

  66. Vanelli M, Chiari G, Ghizzoni L, Costi G, Giacalone T, Chiarelli F. Effectiveness of a prevention program for diabetic ketoacidosis in children. An 8-year study in schools and private practices. Diabetes Care. 1999;22:7–9.

    Article  PubMed  CAS  Google Scholar 

  67. Vanelli M, Chiari G, Lacava S, Iovane B. Campaign for diabetic ketoacidosis prevention still effective 8 years later. Diabetes Care. 2007;30:e12.

    Article  PubMed  Google Scholar 

  68. Barker JM, Goehrig SH, Barriga K, et al. Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care. 2004;27:1399–404.

    Article  PubMed  Google Scholar 

  69. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002;346:1685–91.

  70. Elding LH, Vehik K, Bell R, et al. Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up. Diabetes Care. 2011;34:2347–52.

    Article  Google Scholar 

Download references

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arleta Rewers.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rewers, A. Current Concepts and Controversies in Prevention and Treatment of Diabetic Ketoacidosis in Children. Curr Diab Rep 12, 524–532 (2012). https://doi.org/10.1007/s11892-012-0307-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-012-0307-2

Keywords

Navigation